Replication of chiral α-hydroxy acid via induction and amplification through an enantioenriched cyanohydrin conglomerate

Abstract

A spontaneous absolute asymmetric synthesis of cyanohydrins has been developed without any external chiral source through the combination of conglomerate formation and solution-phase racemization. This method integrates HCN addition reaction to an aldehyde with subsequent Viedma ripening; consequently, spontaneous deracemization and enantioselective reactive crystallization of cyanohydrins are achieved for the first time. Importantly, the hydrolysis products of the cyanohydrin—namely, the corresponding α-hydroxy acid and hydroxyamide—serve as chiral inducer that direct the handedness of solid-state asymmetric amplification, leading to highly enantioenriched cyanohydrins with matching chirality. This feedback between product formation and asymmetric amplification establishes a reaction network in which chirality is propagated and reinforced across molecular transformations. In combination with cyanohydrin hydrolysis, this system constitutes a chemically coupled process that approaches the replication of chiral α-hydroxy acid and hydroxyamide, key products in abiotic Strecker-type synthesis, and is therefore relevant to the origin of biological homochirality.